ISSN:0271-0749    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

This study compared the long-term (12 months) effectiveness of risperidone (RP) with that of conventional neuroleptics (CNs) in a population with chronic schizophrenia who had shown suboptimal response to CNs. A randomized, open, parallel, multicenter design was used. One hundred eighty-four subjects meeting DSM-IV criteria for schizophrenia were randomly assigned to receive either RP or a CN, and 165 of them completed the follow-up. Outcome measures were taken at 3, 6, and 12 months and included the Positive and Negative Syndrome Scale (PANSS) and the Extrapyramidal Symptom Rating Scale. Within this 12-month follow-up, RP was found to be superior to CNs in terms of both the average change in score from baseline on the PANSS (p= 0.006) and the proportion of good responders (as defined by a 20% decrease in total PANSS scores;p= 0.03). For positive symptoms, the effectiveness of the RP treatment tended to increase over time. At 12 months, the percentage of good responders in the RP group was twice as large as that in the CN group (30% vs. 15%;p= 0.03). The superiority of RP over CNs was constant over the three dose categories. In both the RP and the CN groups, the maximum decrease in psychopathology was achieved with the lowest dose range. A worsening of akathisia was less frequent in subjects receiving RP than in those receiving CNs (p= 0.02). In conclusion, this study showed that, compared with CNs, RP is beneficial in the treatment of patients with chronic schizophrenia and that some of these benefits may appear only after longer-term treatment.

ISSN:0271-0749    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

A partial blockade of the multiple actions of cocaine is one strategy by which cocaine dependence may be treated. Risperidone, a 5-hydroxytryptamine and dopamine D2antagonist, is an atypical antipsychotic and was a candidate medication for the treatment of cocaine dependence. One hundred ninety-three cocaine-dependent subjects were enrolled in a 12-week, randomized, double-blind, placebo-controlled trial. Subjects initially received either placebo or 4 or 8 mg of risperidone, with a subsequent change to active doses of 2 mg and 4 mg. Subjects attended the clinic twice each week, provided urine samples, obtained medication, and underwent one behavioral therapy session per week. The study was terminated at the interim analysis. Retention was worse for the 4- and 8-mg active medication groups. Side effects were primarily associated with the 8-mg dose, although neither 2 mg nor 4 mg was well accepted by subjects. There was no reduction in cocaine use associated with risperidone. The results suggest that although antagonists might be a useful treatment approach, such as in the treatment of opiate dependence, risperidone is unlikely to find broad acceptance with the treatment-seeking population.

ISSN:0271-0749    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

This study evaluated anticholinergic effects among patients with schizophrenia, schizoaffective disorder, or bipolar I disorder who were receiving either olanzapine (N = 12) or clozapine (N = 12) at standard clinical doses in a naturalistic setting. Serum anticholinergic levels were determined in adult male and female subjects using a radioreceptor binding assay. The Udvalg for Kliniske Undersogelser Scale was used to evaluate anticholinergic side effects clinically, and the Mini-Mental State Examination provided a global cognitive measure. Patients had achieved target doses that were stable at the time at which blood samples were obtained, and no other concomitant medicine with known anticholinergic potential was allowed. Patients receiving olanzapine (average dose, 15 mg/day) had serum anticholinergic levels of 0.96 (±0.55) pmol/atropine equivalents compared with levels of 5.47 (±3.33) pmol/atropine equivalents for those receiving clozapine (average dose, 444 mg/day) (p< 0.001). Rates of increased and decreased salivation were significantly more common among the clozapine- and olanzapine-treated patients, respectively, whereas constipation, urinary disturbances, and tachycardia/palpitations were significantly more common among clozapine-treated patients. Neither group showed any global cognitive deficits. Olanzapine-treated patients had serum anticholinergic levels that were less than one fifth those of the clozapine-treated patients. Furthermore, clinical evaluations confirmed that clozapine-treated patients experienced more frequent and severe anticholinergic side effects (except dry mouth). However, none of the patients in either group expressed any desire to discontinue these medications as a result of the anticholinergic side effects.

ISSN:0271-0749    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The authors report in detail the case of a 27-year-old man who experienced sudden cardiac death 2 days after coprescription of the neuroleptic pimozide and the macrolide antibiotic clarithromycin after the documentation of a prolonged QT interval. To determine the prevalence of this interaction, the authors referred to the Spontaneous Reporting System of the Food and Drug Administration and identified one similar case in which clarithromycin was coprescribed with pimozide and sudden cardiac death occurred shortly thereafter. In addition, the search identified 39 cases of cardiac arrhythmia associated with pimozide, 11 with pimozide alone, and 6 with clarithromycin alone, 1 of which had a positive rechallenge. The mechanism of the interaction between clarithromycin and pimozide seems to involve the inhibition of the hepatic metabolism of pimozide by the macrolide. The authors demonstrated that clarithromycin is able to inhibit the metabolism of pimozide in human liver microsomal preparations (Ki= 7.65 ± 1.18 μM) and that pimozide, but not clarithromycin or its primary metabolite, is able to prolong the electrocardiac QT interval in a dose-dependent manner in the isolated perfused rabbit heart. The increase was 9.6 ± 1.1% in male hearts (N = 5) and 13.4 ± 1.2% in female hearts (N = 4) (p< 0.05).

ISSN:0271-0749    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The risk of sudden death during clozapine treatment is controversial. The authors present a review of sudden deaths that occurred at Sha'ar Menashe Mental Health Center between January 1991 and August 1997. The number of cases of deceased inpatients was retrieved from the hospital's computerized database and divided into three groups: sudden death, suicide, and disease-related death. Copies of mandatory reports of sudden death filed with the Ministry of Health were obtained, and the corresponding patient records were reviewed. The rates of sudden death, suicide, and disease-related deaths were calculated for clozapine-treated patients (CTPs) during and after treatment and for patients treated with other psychiatric agents (non-CTPs). Among 561 CTPs, there were 4 sudden deaths during treatment, 2 sudden deaths after treatment, 2 suicides during treatment, and 2 disease-related deaths during treatment. Among 4918 non-CTPs, there were 14 sudden deaths, 5 suicides, and 86 disease-related deaths, all of which occurred during treatment with other psychiatric agents. CTPs who experienced sudden death were 10.37 years younger and healthier than non-CTPs who experienced sudden death. The sudden death rate was 3.8 times higher for CTPs than for non-CTPs, whereas the rate of disease-related death was 5 times higher for non-CTPs than for CTPs. Contrary to expectations, the rate of suicide among patients currently receiving clozapine in this sample was 3.6 times higher than among non-CTPs. Because CTPs who experienced sudden death were also younger and healthier, it seems that treatment with clozapine may present a greater risk for sudden death than treatment with other psychiatric medications. The limited number of sudden death cases and deaths from other causes should be noted so that these findings are considered with caution.

ISSN:0271-0749    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Twenty-four healthy male and female subjects, who participated in this randomized, double-blind, crossover study, received single nighttime doses of zaleplon 10 mg (therapeutic dose), zaleplon 20 mg, zolpidem 10 mg (therapeutic dose), zolpidem 20 mg, triazolam 0.25 mg (positive control), and placebo. Subjective behavioral ratings and psychomotor tests were completed before and 1.25 and 8.25 hours after administration of the study drug. The Immediate and Delayed Word Recall tests and the Digit Span Test were used to assess memory. The Digit-Symbol Substitution Test, Paired Associates Learning Test, and Divided Attention Test were used to assess other cognitive skills. Zaleplon 10 mg did not produce any significant changes in memory or learning compared with placebo. All other active treatments, including zolpidem 10 mg, caused psychomotor impairment at the 1.25-hour test battery. Zolpidem 20 mg (twice the therapeutic dose) produced more psychomotor impairment at the 1.25-hour assessment than did any of the other active treatments, including zaleplon 20 mg. At the 8.25-hour time point, test scores for subjects who received zaleplon 10 mg and 20 mg did not differ from the test scores for those who received placebo. However, cognitive impairment persisted up to the 8.25-hour observation for subjects who were administered triazolam 0.25 mg and zolpidem 20 mg. Adverse events associated with the use of zaleplon were transient and mild-to-moderate in severity. Overall, this study shows that zaleplon is a safe hypnotic that does not affect memory, learning, or psychomotor skills associated with vigilance.

ISSN:0271-0749    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The pharmacokinetics and pharmacodynamics of the benzodiazepine alprazolam (1 mg, administered orally) were compared between eight patients with panic disorder and eight age- and sex-matched healthy volunteers. Subjects received orally administered placebo and alprazolam in a randomized, double-blind, single-dose crossover study. The elimination half-life, time of maximum plasma concentration, maximum concentration, volume of distribution, and clearance of alprazolam were similar for both groups. For each cohort, alprazolam treatment (vs. placebo) produced significant changes in typical benzodiazepine agonist effects, such as increased sedation and impaired cognitive performance on the digit-symbol substitution test. For the panic disorder group only, there was a significant increase in the subjective rating of "contented" and a reduction in the rating of "easily irritated." For the healthy volunteer group, alprazolam produced increases in ratings of "fatigued" and "slowed thinking," but also increases in ratings of "relaxed." In each group, alprazolam significantly increased the electroencephalographic (EEG) measure of relative beta amplitude (range, 13-30 Hz) compared with placebo. Concentration-EEG response curves fit a sigmoid Emaxmodel, and there was greater sensitivity to EEG effects, as measured by a 28% reduction in the EC50value, in the panic disorder group compared with healthy control subjects. After alprazolam treatment, there was increased sensitivity to EEG and mood effects and fewer aversive effects in the panic disorder group compared with healthy subjects. There were no differences in the pharmacodynamic measures of sedation and cognition or differences in pharmacokinetics between the two groups.

ISSN:0271-0749    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Six adults phenotyped as either extensive (N = 4) or poor (N = 2) metabolizers for cytochrome P450 (CYP) 2D6 were given a 10-mg oral dose of methylphenidate (MPH) on two separate occasions with and without quinidine, a potent CYP2D6 inhibitor. Quinidine had no significant effect on the pharmacokinetics of either MPH or ritalinic acid, its major metabolite, in either group of CYP2D6 metabolizers. These data suggest a lack of involvement of CYP2D6 in the metabolism of MPH. Drugs that are inhibitors of CYP2D6 when taken concurrently with MPH should not affect its plasma concentration.

ISSN:0271-0749    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Cognitive dysfunction occurs in up to 65% of patients with multiple sclerosis (MS), but there is no effective treatment for the symptoms. The authors conducted a 12-week, open-pilot study to assess the efficacy and tolerability of donepezil HCl administered in patients with MS and cognitive impairment. Seventeen patients at a long-term care facility with Mini-Mental State Examination scores of ≤ 25 received 5 mg of donepezil HCl for a 4-week period, followed by 8 weeks of 10 mg of donepezil HCl. Cognitive, neurologic, functional, and behavioral assessments were conducted at baseline and at 4 and 12 weeks. Statistically significant improvement was observed in several cognitive domains including attention, memory, and executive functioning, as well as different aspects of behavior. These data suggest that donepezil HCl merits further study as a potentially viable treatment option for patients with cognitive impairment associated with MS.

ISSN:0271-0749    

出版商:OVID    

年代:2000

数据来源: OVID